A Phase II Evaluation of Sunitinib Malate (Sutent®, SU11248, NCI-Supplied Agent , NSC # 736511) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus
A Phase II Evaluation of Sunitinib Malate (Sutent®, SU11248, NCI-Supplied Agent , NSC # 736511) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus
This phase II trial is studying how well sunitinib works in treating patients with recurrent or persistent leiomyosarcoma of the uterus. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PRIMARY OBJECTIVES:
I. Assess the activity of sunitinib malate, in terms of rate of progression-free survival for ≥ 6 months and objective tumor response, in patients with recurrent or persistent leiomyosarcoma of the uterus who have received 1 or 2 prior cytotoxic therapies.
II. Determine the frequency and severity of adverse events.
SECONDARY OBJECTIVES:
I. Determine the duration of progression-free survival and overall survival.
OUTLINE: This is a multicenter study. Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Inclusion Criteria:
Histologically confirmed leiomyosarcoma of the uterus
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
Must have ≥ 1 target lesion to assess response
Received at least 1 but no more than 2 prior cytotoxic regimens
Not a candidate for a higher priority GOG protocol
No known brain metastases
GOG performance status 0-2 (for patients who have received 1 prior regimen) OR GOG 0-1 (for patients who have received 2 prior regimens)
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
SGOT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 1.5 times ULN
QTc < 500 msec
LVEF normal by echocardiogram
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment
Patients with a pre-existing thyroid abnormality unable to maintain normal thyroid function with medication are not eligible
No significant EKG abnormalities (i.e., no history of serious ventricular arrhythmia OR EKG with ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
No sensory or motor neuropathy > grade 1
No NYHA class III-IV congestive heart failure
No active infection requiring antibiotics
No other invasive malignancies within the past 5 years except for nonmelanoma skin cancer
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
No gastrointestinal tract disease resulting in an inability to take oral medication
No requirement for IV alimentation
No active peptic ulcer disease
No other condition that would impair ability to swallow and retain study drug
No serious or nonhealing wound, ulcer, or bone fracture
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No cerebrovascular accident or transient ischemic attack within the past year
No myocardial infarction, cardiac arrhythmia, stable or unstable angina, or symptomatic congestive heart failure within the past year
No pulmonary embolism within the past year
No uncontrolled illness including, but not limited to, any of the following:
Recovered from prior surgery, chemotherapy, or radiotherapy
Prior anthracycline exposure and central thoracic radiation that included the heart allowed provided patient has New York Heart Association (NYHA) class II cardiac function
At least 1 week since prior hormonal therapy
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) or radiotherapy
At least 4 weeks since prior major surgery
At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and no recurrent or metastatic disease
At least 3 years since prior adjuvant chemotherapy for localized cancer of the breast and no recurrent or metastatic disease
No prior radiotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma
No prior chemotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma
No prior noncytotoxic chemotherapy for recurrent or persistent disease
No prior surgical procedures affecting absorption
No coronary or peripheral artery bypass graft or stenting within the past year
No other prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or vascular endothelial growth factor [VEGF] Trap)
No other prior cancer treatment that would preclude study treatment
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
No concurrent proarrhythmic potential agent, including any of the following:
No concurrent therapeutic coumarin-derivative anticoagulants, such as warfarin
No concurrent amifostine or other protective agents
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No other concurrent anticancer agents or therapies